Biodegradable polymeric nanoparticles have been intensively studied as a possible way to reduce drug toxicity and degradation, while enhancing the residence time and drug concentration at the desired site of action (K. S. Soppimath, T. M. Aminabhavi, A. R. Kulkarni, W. E. Rudzinski, Biodegradable polymeric nanoparticles as drug delivery devices, J. Control. Release 70 (1-2) (2001) 1-20; J. Panyam, V. Labhaserwar, Biodegradable nanoparticles for drug and gene delivery to cells and tissue, Adv. Drug Deliv. Rev. 55 (3) (2003) 329-347; A. Kumari, S. K. Yadav, S. C. Yadav, Biodegradable polymeric nanoparticles based drug delivery systems, Colloids Surf. B: Biointerfaces 75 (1) (2010) 1-18). Biodegradability is an important attribute of a nanoparticle carrier for several reasons, including the ability to control-release the bound molecule in a sustained, programmable way, and to provide the means for the final removal of the carrier from the body in an innocuous form. Several biodegradable polymers have been used for this application: polylactides (PLA), co-polymers of lactic/glycolic acids (PLGA) and poly(alkylcyanoacrylates) (PACA) are among the most widely investigated for drug delivery. For these systems, two degradation pathways have been identified: the erosion of poly(hydroxy acids) due to a main chain scission mechanism and the PACA biodegradation by side chain cleavage (V. Lenaerts, P. Couvreur, D. Christiaens-Leyh, E. Joiris, M. Roland, B. Rollman, P. Speiser, Degradation of poly(isobutyl cyanoacrylate) nanoparticles, Biomaterials 5 (2) (1984) 65-68: R. H. Müller, C. Lherm, J. Herbort, P. Couvreur, In vitro model for the degradation of alkylcyanoacrylate nanoparticles, Biomaterials 11 (8) (1990) 590-595; J. M. Anderson, M. S. Shive, Biodegradation and biocompatibility of PLA and PLGA microspheres, Adv. Drug Deliv. Rev. 28 (1) (1997) 5-24; M. L. T. Zweers, G. H. M. Engbers, D. W. Grijpma, J. Feijen, In vitro degradation of nanoparticles prepared from polymers based on DL-lactide, glycolide and poly(ethylene oxide), J. Control. Release 100 (3) (2004) 347-356).
Release of entrapped molecules from within the matrix occurs mainly with polymer degradation, as has been reported for poly(hydroxy acid) nanoparticles (J. M. Anderson, M. S. Shive, Biodegradation and biocompatibility of PLA and PLGA microspheres, Adv. Drug Deliv. Rev. 28 (1) (1997) 5-24). Moreover, it has been shown that PLA and PLGA nanoparticles significantly affect the viability of human granulocytes (R. H. Mailer, S. Maaben, H. Weyhers, F. Specht, J. S. Lucks, Cytotoxicity of magnetite-loaded polylactide, polylactide/glycolide particles and solid lipid nanoparticles, Int. J. Pharm. 138 (1) (1996) 85-94). The PACA polymers are non-polar and more effective at entrapping hydrophobic compounds within the nanoparticles matrix, and reportedly degrade rapidly. However, toxicity in human fibroblasts due to byproducts resulting from degradation of the PACA backbone has been reported (C. Lherm, R. H. Müller, F. Puisieux, P. Couvreur, Alkylcyanoacrylate drug carriers: II. Cytotoxicity of cyanoacrylate nanoparticles with different alkyl chain length, Int. J. Pharm. 84 (1) (1992) 13-22).
Polystyrene nanoparticles have also been investigated, and likewise found to entrap lipophilic compounds to a greater extent compared to poly(hydroxy acids) nanoparticles (D. A. Norris, N. Puri, M. E. Labib, P. J. Sinko, Determining the absolute surface hydrophobicity of microparticulates using thin layer wicking, J. Control. Release 59 (2) (1999) 173-185; M. C. Venier-Julienne, J. P. Benoit, Preparation, purification and morphology of polymeric nanoparticles as drug carriers, Pharm. Acta Helv. 71 (2) (1996) 121-128). This can be attributable to their more hydrophobic nature, which may be reinforced by aromatic interactions between pairs of benzene rings in polystyrene (J. W. Longworth, F. A. Bovey, Conformations and interactions of excited states. I. Model compounds for polymers, Biopolymers 4 (10) (1966) 1115-1129). The higher encapsulation of polystyrene nanoparticles could be also attributed to stabilizing π-π interactions between its phenyl groups and heteroaromatic compounds (K. Lee, J. Hong, Nonionic adsorption of aromatic amino acids on a cation-exchange resin, React. Funct. Polym. 28 (1) (1995) 75-80).
While the prior art nanoparticles can efficiently entrap lipophilic compounds, there are still problems with the nanoparticles degrading and producing by-products that may affect biological structures. Additionally, some of the prior art nanoparticles degrade very rapidly thus flooding the subject with the pharmaceutical agent encapsulated within the nanoparticle. A slow controlled release is not possible with the nanoparticles of the prior art. Given the shortcomings of the prior art, what is needed is a chemically-stable biochemically-degradable nanoparticle that can efficiently entrap lipophilic substrates.